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We compared metabolic parameters of skeletal muscle from global <jats:italic>Zip14<\/jats:italic> knockout (KO) and wild-type mice (WT). At basal steady state <jats:italic>Zip14<\/jats:italic> KO mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qPCR analysis of gastrocnemius muscle RNA revealed that ablation of <jats:italic>Zip14<\/jats:italic> produced increased muscle <jats:italic>p-Mef2c<\/jats:italic>, <jats:italic>Hspb7<\/jats:italic> and <jats:italic>miR-675-5p<\/jats:italic> expression and increased p38 activation. ChIP assays showed enhanced binding of NF-<jats:inline-formula><jats:alternatives><jats:tex-math>$$\\kappa \\beta $$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>\u03ba<\/mml:mi><mml:mi>\u03b2<\/mml:mi><\/mml:math><\/jats:alternatives><\/jats:inline-formula> to the <jats:italic>Mef2c<\/jats:italic> promoter. In contrast, LPS-induced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced <jats:italic>MyoD<\/jats:italic>. These signatures of muscle atrophy and cachexia were not influenced by <jats:italic>Zip14<\/jats:italic> ablation, however. LPS-induced <jats:italic>miR-675-3p<\/jats:italic> and <jats:italic>-5p<\/jats:italic> expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesis through suppression of metabolic endotoxemia and that <jats:italic>Zip14<\/jats:italic> ablation coincides with sustained activity of phosphorylated components of signaling pathways including p-Mef2c, which causes Hspb7-dependent muscle wasting.<\/jats:p>","DOI":"10.1038\/s41598-020-61059-2","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T11:02:30Z","timestamp":1583319750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7"],"prefix":"10.1038","volume":"10","author":[{"given":"Jinhee","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolunay Beker","family":"Aydemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix R.","family":"Jimenez-Rondan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney H.","family":"Ruggiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Cousins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"61059_CR1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/0026-0495(82)90108-1","volume":"31","author":"AK Babcock","year":"1982","unstructured":"Babcock, A. 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